E. Gudmand-høyer

Symptoms and Haematologic Features in Consecutive Adult Coeliac Patients

BACKGROUND The aim of this study was to determine in a homogeneous adult population from Denmark, which is known to have very low incidence rates of coeliac disease, 1) the percentage of patients presenting with mild or atypical symptoms; 2) a possible change in clinical pattern over time; and 3) the delay in diagnosis and the age and sex distribution. METHODS The symptoms, delay in diagnosis, age, sex, and haematologic features of 50 consecutive adult coeliac patients, diagnosed by the same person in a uniform manner, are presented. RESULTS The median age was 40.5 (range, 17-82) years. The male to female sex ratio was 1:2.8. The median delay in diagnosis was 3 years. Fifty-eight per cent reported symptoms that could be attributed to coeliac disease during childhood. Presenting symptoms were tiredness, 78%; borborygmus, 72%; abdominal pain, 64%; diarrhoea, 56%; weight loss, 44%; vomiting, 16%; constipation, 12%; bone pain, 12%; and dermatitis herpetiformis, 10%. Weight gain after treatment was experienced by 84%. As a group the coeliac patients had many abnormal blood analysis results, but many patients had several test results inside the normal range. Only 22% had anemia. Liver involvement was not an uncommon feature (19% had increased transaminase levels). Low values were registered in s-iron (32%), p-folate (49%), c-folate (35%), p-vitamin B12 (11%), p-coagulation factors (II, VII, X) (32%), s-protein (21%), s-albumin (26%), s-calcium (43%), p-magnesium (13%), and s-zinc (31%). High/low IgG levels were 3%/8%; high, IgA 21%; high/low IgM, 65%/14%; and high IgE, 71%. The gliadin antibody test was the best screening test (81% positive). No changes in clinical pattern were demonstrated during the period. CONCLUSION The percentage of patients presenting with anaemia (22%) and other haematologic signs of malabsorption was one of the lowest reported ever. This emphasizes the highly variable and subtle clinical expression of adult coeliac disease.

Specific Small-intestinal Lactase Deficiency in Adults

LTT and/or small intestinal biopsy with disaccharidase activity assay was performed in 700 out of 1,300 adult patients at two gastroenterological units. Of 18 patients with specific lactase deficiency only 4 had a history of a previous acute gastrointestinal disease. 17 patients had apparent clinical symptoms, but only 8 had spontaneously observed relation between symptoms and milk intake. In many patients small amounts of milk were sufficient to provoke symptoms, and although dietary treatment was successful, rigorous exclusion of lactose was sometimes necessary.

Incidence and Prevalence of Adult Coeliac Disease within a Defined Geographic Area in Denmark

BACKGROUND In childhood coeliac disease highly varying incidence rates have recently been disclosed. Very low incidence rates (0.09/1000) were found in Denmark, in contrast to our neighbouring country Sweden (2.93/1000). Whether this was accounted for by the diagnosis being delayed until adult life was unknown. No studies concerning the epidemiology of adult coeliac disease in Denmark have been published so far. METHODS The annual incidence rates of adult coeliac disease were determined in the county of Copenhagen during the years 1976-91. The risk of having developed coeliac disease in adult life, on the basis of age and sex, was calculated. The life time prevalences by 5-year birth cohorts were calculated. RESULTS The overall incidence had been stable during the period and was 1.27/10(5). The figures for females and males were 1.55/10(5) and 0.96/10(5), respectively (p = 0.04). The median (range) age at the time of diagnosis was 40.1 (16-81) years. Age-specific incidence rates varied considerably, with the peak rate located in the middle-aged population. Low incidence rates were demonstrated in teenagers and young adults, and increasing rates was seen again in old age. The incidence rates were influenced by age at diagnosis (p = 0.01) and sex (p = 0.04) but not by the year when diagnosed. For a subject aged 89 years the risk was 0.88/1000. The corresponding figures for males and females, were 0.75/1000 and 1.0/1000, respectively. The overall prevalence was 45.9/10(5); males and females, 35.3/10(5) and 55.8/410(5), respectively. CONCLUSION This incidence/prevalence is one of the lowest reported and is definitely lower than prevalences reported in our neighbouring Scandinavian countries. Nothing points to higher incidence rates being present in Danish adults to compensate for the previously demonstrated very low rates in Danish children.

Carbohydrate Malabsorption: Quantification by Methane and Hydrogen Breath Tests

BACKGROUND Previous studies in small series of healthy adults have suggested that parallel measurement of hydrogen and methane resulting from gut fermentation may improve the precision of quantitative estimates of carbohydrate malabsorption. Systematic, controlled studies of the role of simultaneous hydrogen and methane measurements using end-expiratory breath test techniques are not available. METHODS We studied seven healthy, adult methane and hydrogen producers and seven methane non-producers by means of end-expiratory breath test techniques. Breath gas concentrations and gastrointestinal symptoms were recorded at intervals for 12h after ingestion of 10, 20 and 30 g lactulose. RESULTS In the seven methane producers the excretion pattern was highly variable; the integrated methane responses were disproportional and not reliably reproducible. However, quantitative estimates of carbohydrate malabsorption on the basis of individual areas under the methane and hydrogen excretion curves (AUCs) tended to improve in methane producers after ingestion of 20 g lactulose by simple addition of AUCs of methane to the AUCs of the hydrogen curves. Estimates were no more precise in methane producers than similar estimates in non-producers. Gastrointestinal symptoms increased significantly with increasing lactulose dose; correlation with total hydrogen and methane excretion was weak. CONCLUSIONS Our study suggests that in methane producers, simple addition of methane and hydrogen excretion improves the precision of semiquantitative measurements of carbohydrate malabsorption. The status of methane production should, therefore, be known to interpret breath tests semiquantitatively. The weak correlation between hydrogen and methane excretion and gas-related abdominal complaints suggests that other factors than net production of these gases may be responsible for the symptoms.

The Diagnostic Value of the D-Xylose Absorption Test in Adult Coeliac Disease

The 25-g D-xylose absorption test was assessed in a total of 40 adult patients with coeliac disease before and after treatment and in 25 control patients. Because of a large overlap neither the urinary excretion rates nor the 1-h blood concentrations were of any use in the assessment of the individual patients. The overlap was most pronounced for the urine values. In contrast to an earlier report, we could not demonstrate an increased discrimination when the blood concentrations were corrected to a constant body surface area. The D-xylose absorption test provides very little guidance in determining the effect of dietary treatment in coeliac disease. Our results emphasize the serious limitations of the test, and we recommend that it be abandoned.

Evaluation of the Gliadin Antibody Test for Diagnosing Coeliac Disease

The purpose of this study was to evaluate the diagnostic value of gliadin antibodies (GA) in coeliac disease. The test was a diffusion in gel enzyme-linked immunosorbent assay (DIG-ELISA), with combined determination of IgA and IgG. The sensitivity, specificity, and positive and negative predictive value of the test were determined, as used on a well-described, consecutive material of 100 adult patients, admitted for small-intestinal biopsy. For comparison, the positive predictive value of the test, when used on a larger Danish patient material of adults and children, was determined. One hundred and eighteen adults and 55 children with increased or borderline GA were included. For adults the positive predictive value was 71-90%, the negative predictive value 97%, sensitivity 77%, and specificity 95%. For children the positive predictive value was 74%. A graded interpretation, improving the usefulness of the test, is proposed. It is concluded that GA are useful in screening for coeliac disease (CD). It is still necessary to perform at least one small-intestinal biopsy to establish the diagnosis. Highly elevated GA levels strongly indicate CD, whereas a result well below limits makes CD unlikely.

Assimilation of Wheat Starch in Patients with Chronic Pancreatitis Positive Effect of Enzyme Replacement

Pancreatic insufficiency due to chronic pancreatitis may lead to symptomatic malabsorption of both starch and fat. The absorption capacity of wheat starch has not been studied previously in patients with chronic pancreatitis, although this carbohydrate is a quantitatively important component of the Western diet. We studied the absorption of wheat starch and the effect of pancreatic enzyme substitution in seven patients with chronic pancreatitis and steathorrea. The malabsorption was determined from hydrogen breath tests with lactulose standards as reference. Without enzyme substitution, wheat starch (50 g) was absorbed to a lesser extent than in healthy controls (p less than 0.05). The mouth-to-cecum transit time was prolonged and correlated positively to the fat excretion before substitution with pancreatic enzymes (sigma = 1). The enzyme substitution increased the absorption of wheat starch to values seen in healthy controls (p less than 0.05) and reduced the mouth-to-cecum transit time by 19.8%.

Supposed Coeliac Disease during Childhood and Its Presentation 14–38 Years Later

Thirty-five subjects treated with a gluten-free diet for a chronic gastrointestinal disorder (no biopsy performed) in early childhood were re-examined 14-38 (median, 28) years later. Twenty-one accepted jejunal biopsy at re-examination. None of those studied were on a gluten-free diet at the time of the study. Ten of 21 biopsy specimens were abnormal--6 with flat mucosa and very low disaccharidase levels, indicating coeliac disease, and 4 with low disaccharidase activity but morphologically normal mucosa. Three of the six subjects with flat mucosa showed a slight fat and lactose malabsorption, but their clinical condition did not suggest serious intestinal disease. Ingestion of gluten throughout most of childhood did not appear to affect growth, as evaluated by final height. Jejunal biopsy is recommended in all patients with gastrointestinal symptoms that are not otherwise explainable if their medical history shows a period of gluten-free diet for a chronic gastrointestinal disorder in childhood.

Absorption of Wheat Starch in Patients Resected for Left-Sided Colonic Cancer

Bacterial fermentation of carbohydrate in the colon, producing short-chain fatty acids (SCFA)--and especially butyrate--has been shown possibly to impede cell proliferation and regulate cell differentiation of colonocytes. In patients with diverticular disease or benign polyps in the colon a hyperabsorption of potato starch in the small intestine has been found. We have investigated the absorption of wheat starch in 15 patients radically resected for cancer in the descending or sigmoid colon, and the results were compared with those of 15 healthy controls. The starch malabsorption was quantified by the hydrogen breath test. The patients malabsorbed 2-14 g (median, 8 g) of 100 g wheat starch ingested, and the control group malabsorbed 3-11 g (median, 6 g) (P greater than 0.1). Mouth-to-cecum transit time for wheat starch and lactulose and the hydrogen production capacity after the lactulose standards were also similar in patients and controls. The results do not support the theory that hyperabsorption of starch is characteristic of patients with malignant disease in the large intestine.

Growth in Children with Partially Treated Coeliac Disease

Childhood coeliac disease (CD) is often associated with short stature, which may be its only clinical manifestation (1). Karlberg et al. have recently reported their observations on infantile growth in a number of children with CD (2). Their study shows that catch-up growth, initiated after introduction of a gluten-free diet resulted, within a few years, in an average attained height similar to that of controls. Most of us believe that a strict gluten-free diet is necessary for children with CD in order to avoid later growth retardation. Children with a diagnosis of CD are nowadays treated with a gluten-free diet throughout childhood, therefore observation of spontaneous growth in untreated or partially treated childhood CD is not possible. However, a follow-up study of 21 individuals 14-38 years after the initial onset of a chronic childhood gastrointestinal disorder has given us the opportunity to make a retrospective investigation. The 21 subjects were originally presumed to have CD, but no biopsy was performed at the time of the original diagnosis (3). All subjects were initially treated with a gluten-free diet, but were allowed to discontinue the diet when they were feeling well and had obtained catch-up growth. Six had a completely avillous small intestinal rnucosa at the time of follow-up and were classified as CD-patients. The approximate duration of gluten-free diet in childhood for these 6 patients ranged between 3 months and 2-3 years (based upon information from the parents). Data concerning height were available for the time of diagnosis (though not later in childhood) and for the time of follow-up. Deviations of initial and final beights from mean values of agecorrelated longitudinally observed normal children (4) were calculated and compared (Fig. 1). The growth of a child tends to be parallel to the SD lines of a growth chart. The 95% confidence limits for adult height, predicted by such means, are approximately 5 7 cm, corresponding to f l SD (5 ) . Therefore, we expected deviations from mean values either to remain unchanged with age or to increase further in negative direction as a consequence of prolonged gluten intake. This